1. Field of the Invention
The invention relates to a method and apparatus for delivering an agent into cells at a treatment site.
2. Description of the Background
Depending on the type of treatment that is being provided for a patient, systemic administration of medication can produce adverse or even toxic side effects. Local delivery can be the preferred method of treatment in that smaller total levels of medication are administered in comparison to systemic dosages, but are concentrated at a specific site. Local delivery thus produces fewer side effects and achieves more favorable results. Local delivery of medication is particularly advantageous when the treatment site is an isolated region with a biological lumen, such as a blood vessel.
Catheter-based drug delivery systems have been used to locally deliver therapeutic substances to a treatment site. Delivery catheters are generally characterized by an elongate polymeric tube having a lumen in fluid communication with a diffusion port for local delivery of therapeutic agents. One example of such a system is disclosed in U.S. Pat. No. 5,336,205 to Zenzen. Zenzen discloses an infusion catheter with an elongate tubular body having proximal and distal ends and a lumen extending between the ends through which a diagnostic, therapeutic, or vasoocclusive agent can be delivered.
Some medical conditions may require both a balloon catheter and a fluid delivery catheter to facilitate treatment. Catheter systems have been disclosed having a fluid delivery port as well as at least one inflatable balloon. For example, U.S. Pat. No. 5,415,636 to Forman teaches a dilation-drug delivery catheter including a dilation portion for dilating a stenosis and a drug delivery portion for delivering antithrombolytic, antiproliferative, or any other type of medication, to the dilation site. The drug delivery portion of the catheter is located within the dilation portion, which can be retracted to reveal the drug delivery portion after dilation.
U.S. Pat. No. 5,413,581 to Goy dislcoses a balloon dilatation catheter having a first lumen extending along the entire length of a shaft. The lumen is connected to a pump and, at the distal end of the catheter, to the inside of the balloon. The shaft has an additional lumen which opens outwards via an opening behind the proximal end of the balloon. A measuring apparatus or an apparatus for introducing a contrast medium or drug can be connected to this additional lumen.
The above-described catheter-based delivery systems bathe the diseased tissue in a composition containing the therapeutic substance or agent. Cells have a natural resistance to the passage of exogenous molecules through the cell membrane into the interior of the cells. Depending on the biological mechanism targeted, however, the therapeutic substance or agent may be most effective when acting from within the cells of the diseased tissue. Accordingly, intracellular introduction of a therapeutic substance or agent is desirable.
In accordance with one aspect of the present invention, a method of intracellular delivery of an agent is provided. The method includes positioning a catheter having a pair of needle electrodes thereon at a treatment site and causing the needle electrodes to penetrate in tissues of the treatment site. An agent is introduced through at least one of the needle electrodes to the treatment site. An electric field is applied to the treatment site by the pair of electrodes to increase permeability of the cell membranes of cells at the treatment site, wherein the agent passes through the cell membranes into the cells. In some embodiments, applying an electric field causes formation of pores in the cell membranes of the cells at the treatment site, wherein the agent passes through the pores into the cells.
In accordance with another aspect of the present invention, an intraluminal apparatus for introducing an agent into cells at a treatment site is provided. The apparatus includes a catheter assembly for accessing a treatment site through an anatomical lumen and a pair of needle electrodes carried by the catheter assembly. The pair of needle electrodes are in electrical communication with a generator for applying an electric field to the treatment site. At least one needle electrode of the needle electrode pair allows for injection of an agent to the treatment site. In some embodiments, the needle electrodes are retractable into the catheter. In other embodiments, the apparatus includes a retractable sheath that when in an extended position covers the needle electrodes and when in a retracted position exposes the needle electrodes.